A Phase 1b/2a Open Label Bridging Safety, Pharmacokinetics and Tolerability Studies on Chloroquine Based HREZ Combination Regimens in Adults with Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- a) Safety and tolerability of CQ. The assessment includes monitoring clinical manifestations and laboratory abnormalities in the blood.
研究概览
简要总结
Tuberculosis is a persistent and potentially lethal infectious disease caused by Mycobacterium tuberculosis (Mtb), a bacterium that primarily affects the lungs but can also impact other organs. Clinical research on tuberculosis has paved the way for the development and optimization of various drugs aimed at combating this infectious disease. The standard regimen for drug sensitive tuberculosis involves a combination of isoniazid, rifampicin, ethambutol, and pyrazinamide (HREZ), which has been a mainstay in tuberculosis treatment. Chloroquine (CQ), a well-known antimalarial drug, has garnered attention for its potential in the treatment of tuberculosis through preclinical studies.
The rationale for the above study lies in the need to address and optimize tuberculosis treatment strategies, leveraging both established and potential interventions. The inclusion of HREZ, a well-established and effective standard treatment for tuberculosis, serves as a baseline for comparison. Exploring the intake of CQ with HREZ introduces a novel component, aiming to capitalize on CQ’s antiviral properties and immunomodulatory effects. This study seeks to comprehensively evaluate the safety, tolerability, and pharmacokinetics of the CQ based HREZ combination regimen, considering its potential benefits in enhancing the treatment outcome for tuberculosis. By conducting a thorough examination of the risks and benefits associated with both HREZ and CQ, the study endeavours to contribute valuable understandings into refining tuberculosis management strategies, ultimately improving patient outcomes and advancing the field of infectious disease therapeutics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •Adult male and female subjects aged 18 years and above with body weight between 30-65 kg.
- •Individuals who are newly diagnosed with pulmonary tuberculosis through GeneXpert test.
- •Individuals must be previously untreated and test positive for sputum GeneXpert.
- •Subjects must be susceptible to rifampicin as detected by a cartridge-based nucleic acid amplification test.
- •Willingness to undergo HIV testing.
- •Subjects must have never been treated with multidrug antituberculosis therapy for more than a week.
- •Willingness to give blood samples for PK analysis on day 1 and day
- •Willingness to sign the informed consent form and adhere to study procedures and follow-up.
- •Willingness to join the Directly Observed Treatment, Short-Course (DOTS) program 10) Consent to home visits.
排除标准
- •Female subjects who are pregnant, breastfeeding, or planning to conceive during the study.
- •Subjects with extra-pulmonary tuberculosis or drug-resistant tuberculosis (single drug resistance, H, or R).
- •Subjects with a body weight less than 30 kg or greater than 65 kg.
- •Subjects with a prior history of exposure to anti-tuberculosis treatment for more than a week.
- •Subjects with a history of liver disease or current Alanine aminotransferase levels greater than three times the upper limit of normal or total bilirubin concentration exceeding the upper limit of normal.
- •Subjects who test positive for hepatitis B virus surface antigen, hepatitis C virus antibody, and HIV.
- •Subjects with concomitant psychiatric illness or a history of seizures.
- •Anybody testing positive for malaria in the last two months prior to enrolment in the study.
- •Diagnosed cases of extrapulmonary tuberculosis.
- •Subjects who tested positive for COVID-19 with lung involvement.
- •Subjects with malaria and Q-fever undergoing CQ/hydroxy-CQ therapy or have taken CQ/ hydroxy-CQ therapy 2 months prior to enrollment.
结局指标
主要结局
a) Safety and tolerability of CQ. The assessment includes monitoring clinical manifestations and laboratory abnormalities in the blood.
时间窗: Day 0, Day 1, Day 14 & Day 180
b) Overall tolerability of the CQ-based combination regimens will be evaluated by assessing treatment emergent adverse events.
时间窗: Day 0, Day 1, Day 14 & Day 180
次要结局
- a) Pharmacokinetics (PK) Assessment: Establishment of the PK profile of the CQ-based HREZ combination regimen.(b) Safe Dose Determination: Determination of safe CQ dose for the development of a)
研究者
Dr Deepti Krishnan
Hassan Institute of Medical Sciences